Reductions in Aβ-derived neuroinflammation, with minocycline, restore cognition but do not significantly affect tau hyperphosphorylation

Multiple studies have shown that minocycline, a second-generation derivative of tetracycline, is neuroprotective in animal models of central nervous system injury and neurodegenerative diseases. These neuroprotective effects appear to be distinct from the antimicrobial activity of minocycline, but appear to be associated with the ability of minocycline to suppress p38 mitogen-activated protein kinase activity in microglia. Indeed, this minocycline-mediated suppression of p38, in both microglia and other cell types, appears to confer protection in a number of insult models. Previously minocycline has been shown to protect against Aβ-induced neuronal loss in the rat hippocampus, prevent hippocampal long-term potentiation (LTP) deficits induced by Aβ, reduce aggregation of Aβ into fibrils, and improve cognitive deficits in mouse models of AD, and in Aβ infused rats.

In this study the authors investigated the efficacy of minocycline on the AD-like pathology induced inflammation and cognitive decline observed in the 3xTg mouse model of AD. Results showed that minocycline treatment in this model prevents cognitive decline associated with beta amyloid and tau pathologies, reverses the inflammatory response to levels observed in non transgenic littermates, reduces insoluble and fibrillar Aβ, and exhibits differential effects on phosphorylation of tau despite reductions in p25.